A series of ZrO2 supports were treated by ammonia solution with different reflux digestion time, and loaded 25 wt% MoO3 for sulfur-resistant CO methanation reaction by incipient-wetness impregnation method. The MoO3/ZrO2 catalysts were also characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), infrared spectra of adsorbed pyridine (Py-IR). Compared to the undigested ZrO2, ZrO2 with reflux digestion in ammonia solution could achieve more oxygen vacancies, less Lewis acidic sites, smaller crystalline MoO3 and more amount of active sites. Generally, when the support reflux digested in ammonia solution exceed 12 h, the CO conversion of digested catalysts Mo/A-ZrO2-xh reached 60%, while the CO conversion of undigested catalysts was just 36% at the same reaction condition.